Domino cyclization/electrocyclization/elimination reactions of arylacetonitriles with N,N′-bis(1-naphthyl)oxaldiimidoyl dichlorides: Efficient synthesis of fluorescent 15H-benzo[h]benzo[6,7]indolo[3,2-b]quinolines

Article abstract of DOI:10.1002/ejoc.200400405

15H-Benzo[h]benzo[6,7]indolo[3,2-b]quinolines were prepared by domino cyclization/electrocyclization/elimination reactions of nitriles with N,N′-bis(1-naphthyl)oxaldiimidoyl dichlorides. The products can be regarded as hexacyclic δ-carbolines and are novel fluorescent dyes. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400405

FULL PAPER
Domino Cyclization/Electrocyclization/Elimination Reactions of
Arylacetonitriles with N,NЈ-Bis(1-naphthyl)oxaldiimidoyl Dichlorides: Efficient
Synthesis of Fluorescent 15H-Benzo[h]benzo[6,7]indolo[3,2-b]quinolines
Joachim T. Anders[a] and Peter Langer*[a]
Keywords: Domino reactions / Electrocyclic reactions / Nitrogen heterocycles / Synthetic methods
15H-Benzo[h]benzo[6,7]indolo[3,2-b]quinolines were prepa-
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
red by domino cyclization/electrocyclization/elimination re- Germany, 2004)
actions of nitriles with N,NЈ-bis(1-naphthyl)oxaldiimidoyl
dichlorides. The products can be regarded as hexacyclic δ-
carbolines and are novel fluorescent dyes.
δ-Carbolines are of considerable pharmacological rel- available from the reaction of nitriles with oxaldiimidoyl
evance and occur in a variety of natural products.[1Ϫ3] dichlorides.[11,12] Herein we wish to report the direct and
Benzo-annulated δ-carbolines (6H-indolino[3,2-b]quinol- efficient synthesis of 15H-benzo[h]benzo[6,7]indolo[3,2-
ines) can be regarded as isomers of the antitumor agent b]quinolines by domino cyclization/electrocyclization/elim-
ellipticin[4] and are pharmacologically relevant systems due ination reactions of arylacetonitriles with N,NЈ-bis(1-naph-
to their potential cancerostatic activity. We have recently thyl)oxaldiimidoyl dichlorides (Scheme 1).[13] The products,
shown that δ-carbolines selectively bind to triplex or duplex hexacyclic δ-carboline derivatives, are of pharmacological
DNA (intercalation).[5] The 6H-indolino[3,2-b]quinoline relevance and are new fluorescent markers.
core structure occurs, for example, in the natural products
cryptolepine, cryptoquindoline, biscryptolepine and neo-
cryptolepine.[6,7] Cryptolepine and cryptoquindoline were
first isolated from the West African plant Cryptolepis
sanguinolenta and have been used for the treatment of Ma-
laria. Extensive pharmacological studies have shown that
cryptolepine possesses a variety of interesting features, in-
cluding antimicrobial and antifungal activity.[8] The anti-
fungal activity is of interest for the treatment of infections
by the fungus Cryptococcus neoformans.[9] These infections
are dangerous for AIDS patients, due to their weak immune
systems. Cryptolepine has been recently studied[10] as a sub-
stitute for the commonly used drug amphotericin B, which
has a number of side effects.
Scheme 1. Retrosynthetic analysis
Our starting point was the synthesis of N,NЈ-bis(1-naph-
thyl)oxaldiimidoyl dichloride (2). The synthesis was carried
out analogously to the preparation of N,NЈ-diphenyloxaldi-
imidoyl dichloride.[14] The reaction of 1-aminonaphthalene
with diethyl oxalate gave the bis(amide) 1, which was trans-
formed into 2 by chlorination with phosphorus() penta-
chloride (Scheme 2).
The reaction of 2 with dilithiated phenylacetonitrile (3a)
We have recently reported[5] a new and efficient approach
to 6H-indolino[3,2-b]quinolines by electrocyclization reac-
tions of 2-alkylidene-3-iminoindoles, which are readily
afforded the 2-alkylidene-3-iminobenzindole 4a, as a violet
solid in 91% yield. It is assumed that 4a possesses an (E)-
configured double bond based on the structure established
[a]
Institut für Chemie und Biochemie der Ernst-Moritz-Arndt-
Universität Greifswald,
Soldmannstr. 16, 17487 Greifswald, Germany
5020
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400405
Eur. J. Org. Chem. 2004, 5020Ϫ5026

Efficient Synthesis of Fluorescent 15H-Benzo[h]benzo[6,7]indolo[3,2-b]quinolines
FULL PAPER
Scheme 2. Synthesis of N,NЈ-bis(1-naphthyl)oxaldiimidoyl dichlor-
ide
earlier for related 2-alkylidene-3-iminoindoles.[11] The for-
mation of 4a can be explained, in analogy to our recently
published method for the synthesis of 2-alkylidene-3-imino-
indoles,[11] by attack of 3a on 2 to give intermediate A, fol-
lowed by cyclization via the canonical form B and sub-
Scheme 4. Synthesis of 5a by electrocyclization of 4a
sequent aromatization (Scheme 3).
tuted δ-carbolines 5bϪd were prepared from 3bϪd (see
Table 1). The methoxy-substituted product 5e was prepared
from 3e, and the cyclization of (2-naphthyl)methyl cyanide
(3f) with 2 afforded 5f. The nitro-, cyano-, and bromo-
substituted 15H-benzo[h]benzo[6,7]indolo[3,2-b]quinolines
5gϪj were prepared from the corresponding arylmethyl cy-
anides 3gϪj (Table 1). Significantly higher yields were gen-
erally obtained for method B than for method A. All prod-
ucts were formed in good to excellent yields. The use of
LDA allowed the preparation of 2-alkylidene-3-im-
inobenzindoles 4.
Scheme 3. Synthesis of 2-alkylidene-3-iminobenzindole 4a; i: 1) 2.5
equiv. LDA, THF, 0 °C, 2) 2, Ϫ78 Ǟ 20 °C
Reflux of a DMSO solution of 4a resulted in formation
of the 15H-benzo[h]benzo[6,7]indolo[3,2-b]quinoline 5a in
65% yield (Scheme 4). The formation of 5a can be explained
by (E)/(Z) isomerization (intermediate C), electrocyclization
(intermediate D), and subsequent extrusion of hydrogen cy-
anide. The structure of the S-shaped hexacyclic δ-carboline
5a was established by spectroscopic methods. To the best of
our knowledge, the synthesis of 15H-benzo[h]benzo[6,7]in-
dolo[3,2-b]quinolines has not been reported to date.
The two-step synthesis of 15H-benzo[h]benzo[6,7]in-
dolo[3,2-b]quinoline 5a from 2 was accomplished in 59%
overall yield (method A). We have also developed an
alternative approach (Scheme 5): reflux of a THF solution
of 3a and 2 in the presence of sodium hydride directly af-
forded 5a by a domino cylization/electrocyclization/elimin-
Scheme 5. Synthesis of 15H-benzo[h]benzo[6,7]indolo[3,2-b]quinol-
ines 5
The 15H-Benzo[h]benzo[6,7]indolo[3,2-b]quinolines
5
ation reaction (method B). The yield was significantly show a strong fluorescence. Emission in the region 442Ϫ453
higher for the domino reaction (method B, 83%) than for nm is observed for alkyl- and bromo-substituted derivatives.
the two-step synthesis (method A, 59%). The methyl-substi- No shift of the emission wavelength was observed for meth-
Eur. J. Org. Chem. 2004, 5020Ϫ5026
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5021

J. T. Anders, P. Langer
FULL PAPER
troscopy: PerkinϪElmer Lambda 2 and PerkinϪElmer Lambda 19
UV/Vis/NR Spectrometer. The elemental analyses were carried out
at the microanalytical laboratory of the University of Göttingen
(Leco CHN 2000, Heraeus apparatus Mikro U/D). Chromatogra-
phy: Merck silica gel 60 (0.063Ϫ0.200 mm, 70Ϫ230 mesh ASTM)
or Merck silica gel 60 (0.040Ϫ0.063 mm, 230Ϫ400 mesh ASTM).
All solvents were distilled prior to use. TLC: Merck silica gel 60
Table 1. Products and yields
5
Method
R1
R2
R3
Yield (%)[a]
λmax [nm][b]
a
a
b
c
d
d
e
e
f
B
A
B
B
B
A
B
A
B
A
B
B
B
B
H
H
Me
H
H
H
H
H
H
H
H
CN
H
H
H
H
H
Me
H
H
H
H
ϪC4H4Ϫ
ϪC4H4Ϫ
H
H
Br
H
H
H
H
H
Me
Me
OMe
OMe
83
59
98
92
71
27
90
48
89
48
62
96
95
96
447
447
442
446
445
445
442
442
452
452
Ϫ
F254 and MachereyϪNagel Alugram Sil G/UV254
.
N,NЈ-Bis(1-naphthyl)oxalamide (1): A toluene solution (20 mL) of
diethyl oxalate (1.46 g, 10.0 mmol) and 1-aminonaphthalene (2.86
g, 20.0 mmol) was refluxed for 8 h. The precipitate formed was
filtered off and washed with EtOH to give 1 (2.90 g, 85%) as a
colourless solid. M.p. 246.5 °C. IR (KBr): ν˜ ϭ 770 (m), 807 (s),
1493 (s), 1516 (s), 1672 (s), 1686 (s), 3328 (s) cmϪ1. 1H NMR (200
MHz, [D6]DMSO): δ ϭ 7.54Ϫ8.02 (m, 14 H, Ar), 10.91 (s, 2 H,
NH) ppm. 13C NMR (50 Hz, [D6]DMSO): δ ϭ 122.81, 122.83,
125.44, 126.12, 126.15, 126.60, 128.03 (CH), 128.27, 132.42, 133.63,
159.56 (C) ppm. MS (EI, 70 eV): m/z (%) ϭ 340 (79) [M]ϩ, 143
(100), 127 (37), 114 (64). C22H16N2O2 (340.22): calcd. C 77.66, H
4.70, N 8.22; found C 77.47, H 4.57, N 7.94.
f
g
h
i
NO2
H
H
Br
472
453
452
j
[a]
[b]
Yields of isolated products; yield over two steps for method A.
Fluorescence (CH3CN).
oxy-substituted 5e. A bathochromic shift was observed for
cyano-substituted 5h.
The reaction of 1,4-bis(cyanomethyl)benzene with 2 (2
equiv.) in the presence of sodium hydride (6 equiv.) resulted
in the formation of bis(carboline) 6, which is formed as a
result of a double domino cyclization/electrocyclization/ g, 63%). M.p. 187 °C. IR (KBr): ν
N,NЈ-Bis(1-naphthyl)oxaldiimidoyl dichloride (2): A toluene solu-
tion (20 mL) of 1 (3.40 g, 10.0 mmol) and PCl5 (4.16 g, 20.0 mmol)
was refluxed for 4 h. The mixture was concentrated in vacuo and
was cooled to 20 °C to give a precipitate. The latter was filtered off
and recrystallized from n-heptane to give 2 as yellow needles (2.40
˜ ϭ 765 (m), 1490 (w), 1672 (m)
cmϪ1. 1H NMR (200 MHz, CDCl3): δ ϭ 7.30Ϫ7.33 (d, 7 Hz, 2 H,
Ar), 7.51Ϫ7.56 (m, 6 H, Ar), 7.78Ϫ7.80 (d, 7 Hz, 2 H, Ar),
7.78Ϫ7.89 (m, 2 H, Ar), 8.40 (s, 2 H, Ar) ppm. 13C NMR (50 Hz,
CDCl3): δ ϭ 110.55, 123.52, 125.50, 126.72, 126.80, 126.92, 127.38,
128.20, 130.40, 130.90, 140.20 ppm. MS (EI, 70 eV): m/z (%) ϭ
377 (39) [M]ϩ, 188 (100), 153 (29), 127 (63). C22H14N2Cl2 (377.12):
calcd. C 70.06, H 3.71, N 7.42; found C 69.34, H 4.60, N 8.12.
elimination reaction (Scheme 6).
General Procedure for the One-Pot Synthesis of Benzo[g]indol-
ino[3,2-b]benzo[h]quinolines (Method B): Sodium hydride (0.04 g,
1.5 mmol) and N,NЈ-bis(1-naphthyl)oxaldiimidoyl dichloride (2)
(0.19 g, 0.5 mmol) were added to a THF solution (50 mL) of aryla-
cetonitrile 3 (0.5 mmol) and the solution was refluxed for about
12 h (TLC control). An aqueous solution of NH4Cl (250 mL, 1 )
was then added to the mixture. The organic and aqueous layers
were separated and the latter was extracted with dichloromethane
Scheme 6. Cyclization of 1,4-bis(cyanomethyl)benzene with 2
In summary, the domino cyclization/electrocyclization/ (3 ϫ 100 mL). The combined organic layers were dried (Na2SO4)
and the solvent was removed in vacuo. The residue was purified by
chromatography (silica gel; n-pentane/diethyl ether, 10:1) to give
5aϪj as yellow solids.
elimination reaction of nitriles with N,NЈ-bis(1-naphth-
yl)oxaldiimidoyl dichlorides allows a convenient synthesis
of 15H-benzo[h]benzo[6,7]indolo[3,2-b]quinolines, which
can be regarded as hexacyclic δ-carbolines and are novel
fluorescent dyes.
General Procedure for the Two-Step Synthesis of Benzo[g]indol-
ino[3,2-b]benzo[h]quinolines (Method A). Step 1: Synthesis of 3-(Ar-
ylimino)-2-(1-aryl-1-cyanomethylidene)indoles 4: A THF solution of
lithium diisopropylamide (LDA) was prepared as follows: n-butyl-
lithium (1.06 mL, 2.36  solution in n-hexane, 2.50 mmol) was ad-
ded at 0 °C to a THF solution (30 mL) of diisopropylamine (0.23 g,
2.30 mmol). The solution was stirred at 0 °C for 30 min. Com-
pound 3 (1.00 mmol) was added dropwise at 0 °C to this LDA solu-
Experimental Section
General: NMR measurements: Bruker AM 250 (250 MHz), Varian
Unity 200 (200 MHz), Varian Mercury 200 (200 MHz), Varian Un-
ity 300 (300 MHz), Varian Mercury 300 (300 MHz), Bruker AMX tion and the solution was stirred at 0 °C for 60 min. The solution
300 (300 MHz). Mass spectrometry: EI (electron ionization, 70 eV);
DCI (direct chemical ionization, 200 eV, NH3) and HRMS: Finni-
gan MAT 95, ESI (electrospray-ionization): Finnigan LCQ. ESI-
HRMS (high-resolution ESI): APEX IV (Bruker Deltonik) FT-
ICR-MS. Infrared spectroscopy: FT-IR Bruker Vector 22, Bruker
was then cooled to Ϫ78 °C and was added by cannula to a THF
solution (40 mL) of 2 (1.00 mmol) at Ϫ78 °C. The solution was
warmed within 1.5 h to 20 °C. The progress of the reaction was
monitored by TLC. An aqueous solution of NH4Cl (250 mL, 1 )
was then added to the mixture. The organic and aqueous layers
IFS 66, Nicolett 205 FT-IR. Fluorescence spectroscopy: were separated and the latter was extracted with diethyl ether (3 ϫ
PerkinϪElmer Luminescence Spectrometer LS 50B. UV/Vis spec- 100 mL). The combined organic layers were dried (Na2SO4) and
5022
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 5020Ϫ5026

Efficient Synthesis of Fluorescent 15H-Benzo[h]benzo[6,7]indolo[3,2-b]quinolines
FULL PAPER
the solvent was removed in vacuo. The residue was purified by
chromatography (silica gel; petroleum ether/diethyl ether,
10:1Ǟ1:1Ǟ1:10) to give compounds 4 as orange to violet solids.
Step 2: Transformation of 2-Alkylidene-3-iminoindoles 4 into Benzo[-
g]indolino-[3,2-b]benzo[h]quinolines 5: A DMSO solution (25 mL)
(CH), 125.72 (C), 125.82 (CH), 126.23 (C), 126.29, 126.38, 126.46,
127.67, 128.76, 130.05 (CH), 134.34, 135.79, 146.44, 146.85, 146.98,
156.74, 159.94 (C) ppm. IR (KBr): ν˜ ϭ 3328 (s), 3053 (w), 2967
(w), 2199 (m), 1673 (s), 1649 (m), 1640 (m), 1598 (m), 1573 (m),
1516 (s), 1489 (s), 1465 (m), 1438 (m), 1393 (m), 1347 (m), 1322
of 4 (0.25 mmol) was stirred at 150 °C for 4 h. The progress of the (m), 1251 (m), 1204 (m), 1181 (m), 1154 (m), 807 (s), 771 (s), 651
reaction was monitored by TLC. The solvent was then removed in
vacuo and the residue was purified by chromatography (silica gel;
(m), 574 (m) cmϪ1. UV/Vis (CH3CN): λmax (lg ε) ϭ 494.3 nm
(3.36), 293.1 (4.28), 222.0 (4.98). MS (EI, 70 eV): m/z (%) ϭ 451
n-pentane/diethyl ether, 10:1) to give compounds 5 as yellow solids. (4) [M]ϩ, 450 (10) [M Ϫ H]ϩ, 424 (42) [M Ϫ HCN]ϩ, 340 (48), 143
(100). The exact molecular mass (m/z ϭ 451.1685 Ϯ 2 mD [Mϩ])
for C31H21N3O was confirmed by HRMS (EI, 70 eV).
(E)-2-(1-Cyano-1-phenylmethylidene)-3-(1-naphthylimino)-2,3-
dihydro-1H-benzo[g]indole (4a): Starting with phenylacetonitrile
(3a; 0.12 g, 1.00 mmol) and 2 (0.38 g, 1.00 mmol), 4a was isolated (E)-2-[1-Cyano-1-(2-naphthyl)methylidene]-3-(1-naphthylimino)-2,3-
as a violet solid (0.38 g, 91%, E/Z Ͼ 98:2). 1H NMR (250 MHz,
dihydro-1H-benzo[g]indole (4f): Starting with (2-naphthyl)acetoni-
[D6]DMSO): δ ϭ 6.65 (d, 3J ϭ 8.7 Hz, 1 H, Ar), 6.95 (d, 3J ϭ trile (3f; 0.17 g, 1.00 mmol) and 2 (0.38 g, 1.00 mmol), 4f was iso-
8.7 Hz, 1 H, Ar), 7.15 (d, 3J ϭ 7.3 Hz, 1 H, Ar), 7.40Ϫ7.93 (m, lated as a violet solid (0.42 g, 89%, E/Z Ͼ 98:2). 1H NMR
15 H, Ar, NH), 8.21 (d, 3J ϭ 7.9 Hz, 1 H, Ar) ppm. 13C NMR
(50.3 MHz, [D6]DMSO): δ ϭ 88.59 (CϪCN), 112.49 (CH), 113.27,
118.99, 119.40 (C), 120.98, 121.90, 124.14, 124.78, 125.64, 125.85
(250 MHz, CDCl3): δ ϭ 6.68 (d, 3J ϭ 8.7 Hz, 1 H, Ar), 6.97 (d,
3
3J ϭ 8.9 Hz, 1 H, Ar), 7.17 (d, J ϭ 7.2 Hz, 1 H, Ar), 7.40Ϫ7.60
(m, 7 H, Ar, NH), 7.67Ϫ7.79 (m, 3 H, Ar), 7.87Ϫ7.96 (m, 5 H, Ar),
(CH), 126.17 (C), 126.33, 126.48, 127.67, 128.66, 128.76, 128.81, 8.04 (d, 3J ϭ 8.6 Hz, 1 H, Ar), 8.23 (d, 3J ϭ 8.0 Hz, 1 H, Ar), 8.25
128.85, 128.88, 129.72 (CH), 133.65, 134.29, 135.80, 146.39, 146.66, (s, 1 H, Ar) ppm. 13C NMR (50.3 MHz, CDCl3): δ ϭ 88.87
147.62, 156.74 (C) ppm. IR (KBr): ν˜ ϭ 3056 (m), 2929 (w), 2198
(CϪCN), 112.55 (CH), 113.41, 119.00, 119.48 (C), 121.01, 121.05,
(m), 1685 (m), 1673 (m), 1635 (s), 1586 (s), 1572 (s), 1525 (s), 1492 121.97, 124.20, 124.83, 125.53, 125.65, 125.90 (CH), 126.25 (C),
(m), 1465 (s), 1447 (s), 1418 (m), 1391 (s), 1346 (m), 1321 (m), 1261 126.35, 126.50, 127.09, 127.23, 127.69, 127.85, 128.25, 128.47,
(m), 1203 (s), 1087 (m), 810 (m), 792 (m), 773 (s), 753 (s) cmϪ1
.
128.79, 129.43, 129.63 (CH), 131.04, 133.02, 133.58, 134.35, 135.84,
UV/Vis (CH3CN): λmax (lg ε) ϭ 492.1 nm (3.89), 350.8 (4.11), 336.5 146.43, 146.73, 147.85, 156.78 (C) ppm. IR (KBr): ν˜ ϭ 3398 (w),
(4.13), 281.4 (4.41), 233.6 (4.62) ppm. MS (ESI): m/z (%) ϭ 865 3053 (w), 2197 (m), 1677 (w), 1637 (s), 1572 (s), 1525 (s), 1464 (m),
(100) [2 M ϩ Na]ϩ, 863 (5) [2 M Ϫ 2 H ϩ Na]Ϫ, 722 (14), 539 (8), 1447 (m), 1417 (m), 1390 (s), 1320 (s), 1204 (s), 1087 (m), 803 (m),
422 (12) [M ϩ H]ϩ, 421 (35) [M]Ϫ, 420 (100) [M Ϫ H]Ϫ, 395 (8) 772 (s), 753 (s) cmϪ1. UV/Vis (CH3CN): λmax (lg ε) ϭ 497.9 nm
[M Ϫ CN]ϩ.
(3.96), 353.6 (4.13), 276.8 (4.49), 221.9 (4.97). MS (ESI): m/z (%) ϭ
965 (100) [2 M ϩ Na]ϩ, 870 (10) [2 M Ϫ 2 H ϩ Na]Ϫ, 494 (15) [M
ϩ Na]ϩ, 471 (28) [M]Ϫ, 470 (100) [M Ϫ H]Ϫ. The exact molecular
mass [M ϩ H]ϩ for C31H21N3 was confirmed by ESI-HRMS: calcd.
472.18082; found 472.18108.
(E)-2-[1-Cyano-1-(4-tolyl)methylidene]-3-(1-naphthylimino)-2,3-
dihydro-1H-benzo[g]indole (4d): Starting with 4-tolylacetonitrile
(3d; 0.07 g, 0.50 mmol) and 2 (0.19 g, 0.50 mmol), 4d was isolated
as a violet solid (0.10 g, 44%, E/Z Ͼ 98:2). 1H NMR (250 MHz,
3
CDCl3): δ ϭ 2.45 (s, 3 H, ArCH3), 6.64 (d, J ϭ 8.8 Hz, 1 H, Ar),
14-Phenyl-15H-benzo[h]benzo[6,7]indolo[3,2-b]quinoline (5a):
6.95 (d, 3J ϭ 8.6 Hz, 1 H, Ar), 7.14 (d, 3J ϭ 7.2 Hz, 1 H, Ar), Method B: Starting with phenylacetonitrile (3a; 0.12 g, 1.00 mmol),
3
7.37Ϫ7.80 (m, 11 H, Ar, NH), 7.90 (t, J ϭ 7.7 Hz, 2 H, Ar), 7.99
5a was isolated as a yellow solid (0.33 g, 83%). Method A: Starting
3
3
(d, J ϭ 8.0 Hz, 1 H, Ar), 8.21 (d, J ϭ 8.0 Hz, 1 H, Ar) ppm. 13C with 4a (0.11 g, 0.26 mmol), 5a was isolated as a yellow solid
NMR (50.3 MHz, CDCl3): δ ϭ 21.35 (ArCH3), 88.89 (CϪCN),
112.53 (CH), 113.38 (C), 119.21 (CH), 119.44 (C), 120.11, 120.95, 11 H, Ar), 7.88 (d, J ϭ 7.8 Hz, 1 H, Ar), 8.03Ϫ8.08 (m, 2 H, Ar),
122.00, 124.20, 124.70, 125.65, 125.85 (CH), 126.18 (C), 126.50,
126.80, 127.68, 128.53, 128.78, 130.39 (CH), 130.72, 134.01, 134.33, 8.2 Hz, 1 H, Ar) ppm. 13C NMR (50.3 MHz, CDCl3): δ ϭ 118.09
135.81, 139.08, 146.42, 146.80, 147.29, 158.15 (C) ppm. IR (KBr): (C), 119.76, 120.64 (CH), 120.80 (C), 121.01 (CH), 122.10 (C),
(0.07 g, 65%). 1H NMR (250 MHz, CDCl3): δ ϭ 7.53Ϫ7.84 (m,
3
8.54 (s, 1 H, NH), 8.66 (d, 3J ϭ 8.6 Hz, 1 H, Ar), 9.73 (d, 3J ϭ
ν˜ ϭ 3430 (s), 3054 (w), 2956 (w), 2201 (m), 1673 (s), 1636 (s), 1635 123.02, 124.74, 125.70, 126.10, 126.52, 126.69, 127.24, 127.51 (CH),
(s), 1589 (m), 1573 (s), 1522 (s), 1490 (m), 1464 (m), 1447 (m), 1392 127.88 (C), 128.76, 129.13, 129.39 (CH), 129.94 (C), 130.23 (CH),
(m), 1344 (m), 1321 (m), 1265 (m), 1203 (s), 1086 (m), 806 (s), 772
132.20, 132.30, 134.00, 134.61, 139.10, 142.72, 143.10 (C) ppm. IR
(s), 754 (m) (cmϪ1). UV/Vis (CH3CN): λmax (lg ε) ϭ 493.0 nm (KBr): ν˜ ϭ 3447 (m), 3052 (m), 1598 (m), 1564 (w), 1532 (m), 1518
(3.75), 351.5 (3.94), 282.7 (4.30), 220.9 (4.81). MS (ESI): m/z (%) ϭ (m), 1490 (m), 1466 (s), 1438 (m), 1420 (w), 1382 (s), 1361 (w),
893 (100) [2 M ϩ Na]ϩ, 870 (10) [2 M Ϫ 2 H]2Ϫ, 797 (8), 458 (12)
1331 (m), 1285 (m), 1195 (s), 1183 (m), 826 (m), 800 (m), 757 (s),
[M ϩ Na]ϩ, 436 (10) [M ϩ H]ϩ, 435 (35) [M]Ϫ, 434 (100) [M Ϫ 738 (w), 699 (m), 671 (m) cmϪ1. Fluorescence (CH3CN): Ex
H]Ϫ. The exact molecular mass [M ϩ H]ϩ for C31H21N3 was con- (Fλmax) ϭ 375 (447.49) nm. UV/Vis (CH3CN): λmax (lg ε) ϭ 381.7
firmed by ESI-HRMS: calcd. 436.18082; found 436.18076.
nm (4.37), 363.2 (4.25), 306.5 (4.79), 260.7 (4.47), 243.5 (4.49). MS
(EI, 70 eV): m/z (%) ϭ 394 (100) [M]ϩ, 340 (4), 197 (20), 143 (5).
The exact molecular mass (m/z ϭ 394.1470 Ϯ 2 mD [Mϩ]) for
C29H18N2 was confirmed by HRMS (EI, 70 eV). C29H18N2
(394.47): calcd. C 88.30, H 4.60, N 7.10; found C 88.22, H 4.87,
N 6.98.
(E)-2-[1-Cyano-1-(4-methoxyphenyl)methylidene]-3-(1-naphthyl-
imino)-2,3-dihydro-1H-benzo[g]indole (4e): Starting with (4-meth-
oxyphenyl)acetonitrile (3e; 0.15 g, 1.00 mmol) and
2 (0.38 g,
1.00 mmol), 4e was isolated as a violet solid (0.33 g, 74%, E/Z Ͼ
98:2). 1H NMR (250 MHz, CDCl3): δ ϭ 3.89 (s, 3 H, OCH3), 6.63
3
3
(d, J ϭ 8.7 Hz, 1 H, Ar), 6.95 (d, J ϭ 8.7 Hz, 1 H, Ar), 7.10 (d,
14-(2-Tolyl)-15H-benzo[h]benzo[6,7]indolo[3,2-b]quinoline (5b):
3J ϭ 8.8 Hz, 2 H, Ar), 7.15 (d, J ϭ 7.4 Hz, 1 H, Ar), 7.41Ϫ7.80 Starting with 2-tolylacetonitrile (3b; 0.07 g, 0.50 mmol), 5b was iso-
3
(m, 11 H, Ar, NH), 7.88 (t, 3J ϭ 8.2 Hz, 1 H, Ar), 8.21 (d, 3J ϭ lated as a yellow solid (0.02 g, 98%). 1H NMR (250 MHz, CDCl3):
7.1 Hz, 1 H, Ar) ppm. 13C NMR (50.3 MHz, CDCl3): δ ϭ 55.46
δ ϭ 2.04 (s, 3 H, ArCH3), 7.40Ϫ7.57 (m, 7 H, Ar), 7.60Ϫ7.85 (m,
(OCH3), 88.82 (CϪCN), 112.54 (CH), 113.48 (C), 115.15 (CH), 4 H, Ar), 7.90 (d, 3J ϭ 7.8 Hz, 1 H, Ar), 8.04 (d, 3J ϭ 7.9 Hz, 1 H,
3
119.05, 119.49 (C), 120.86, 120.97, 122.01, 124.20, 124.65, 125.67
Ar), 8.10 (d, 3J ϭ 7.9 Hz, 1 H, Ar), 8.75 (d, J ϭ 8.6 Hz, 1 H, Ar),
Eur. J. Org. Chem. 2004, 5020Ϫ5026
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5023

J. T. Anders, P. Langer
FULL PAPER
8.81 (br. s, 1 H, NH), 9.81 (d, 3J ϭ 8.1 Hz, 1 H, Ar) ppm. 13C a yellow solid (0.05 g, 65%). 1H NMR (250 MHz, CDCl3): δ ϭ 3.91
3
NMR (50.3 MHz, CDCl3): δ ϭ 19.77 (ArCH3), 118.07 (C), 119.75, (s, 3 H, OCH3), 7.24 (d, J ϭ 8.7 Hz, 2 H, Ar), 7.57Ϫ7.83 (m, 9 H,
3
120.82 (CH), 120.88 (C), 121.02 (CH), 122.55 (C), 123.09, 124.70,
125.67, 126.21, 126.46, 126.50, 126.69, 127.21, 127.55, 128.99,
Ar), 7.96 (d, J ϭ 7.6 Hz, 1 H, Ar), 8.07Ϫ8.11 (m, 1 H, Ar), 8.23
(br. s, 1 H, NH), 8.55 (d, 3J ϭ 8.6 Hz, 1 H, Ar), 8.90Ϫ8.94 (m, 1 H,
129.07 (CH), 130.12 (C), 130.23, 130.76 (CH), 132.23, 132.40, Ar), 9.58 (d, 3J ϭ 7.8 Hz, 1 H, Ar) ppm. 13C NMR (50.3 MHz,
133.77, 134.01, 137.49, 139.24, 142.49, 143.29 (C) ppm. IR (KBr): [D6]DMSO): δ ϭ 55.19 (OCH3), 114.42 (CH), 116.65 (C), 118.91,
ν˜ ϭ 3431 (m), 3051 (m), 2955 (w), 2921 (w), 1631 (w), 1599 (w),
120.36 (CH), 121.34, 122.10 (C), 123.16, 123.22, 124.07, 125.34,
1566 (w), 1531 (m), 1512 (m), 1465 (m), 1451 (m), 1439 (m), 1422 125.41 (CH), 126.04 (C), 126.55, 127.14, 127.52 (CH), 128.25 (C),
(m), 1382 (s), 1330 (m), 1286 (m), 1243 (m), 1196 (m), 1179 (m), 128.50 (CH), 130.43, 131.60 (C), 131.68 (CH), 131.77, 133.64,
829 (m), 802 (m), 761 (s) cmϪ1. Fluorescence (CH3CN): Ex
140.24, 141.28, 142.67, 159.37 (C) ppm. IR (KBr): ν˜ ϭ 3460 (s),
(Fλmax) ϭ 380 (442.49) nm. UV/Vis (CH3CN): λmax (lg ε) ϭ 381.1 3050 (m), 1630 (m), 1608 (s), 1568 (w), 1531 (m), 1509 (s), 1464
nm (4.39), 362.4 (4.26), 322.9 (4.21), 305.8 (4.76), 266.3 (4.44),
(m), 1440 (m), 1382 (s), 1332 (m), 1289 (m), 1247 (s), 1181 (s), 1028
260.4 (4.44), 241.5 (4.48), 216.0 (4.63). MS (EI, 70 eV): m/z (%) ϭ (m), 830 (m), 798 (m), 766 (s), 736 (m), 573 (m) cmϪ1. Fluorescence
408 (100) [M]ϩ, 203 (14), 196 (8), 143 (4). The exact molecular (CH3CN): Ex (Fλmax) ϭ 385 (441.98) nm. UV/Vis (CH3CN): λmax
mass (m/z ϭ 408.1626 Ϯ 2 mD [Mϩ]) for C30H20N2 was confirmed (lg ε) ϭ 381.4 nm (4.40), 363.2 (4.28), 307.7 (4.80), 261.4 (4.49),
by HRMS (EI, 70 eV).
228.6 (4.65), 218.4 (4.67). MS (EI, 70 eV): m/z (%) ϭ 424 (100)
[M]ϩ, 380 (10), 212 (10), 190 (14). The exact molecular mass
(m/z ϭ 424.1576 Ϯ 2 mD [Mϩ]) for C30H20N2O was confirmed by
HRMS (EI, 70 eV).
14-(3-Tolyl)-15H-benzo[h]benzo[6,7]indolo[3,2-b]quinoline (5c):
Starting with 3-tolylacetonitrile (3c; 0.07 g, 0.50 mmol), 5c was iso-
lated as a yellow solid (0.19 g, 92%). 1H NMR (250 MHz, CDCl3):
3
δ ϭ 2.56 (s, 3 H, ArCH3), 7.47Ϫ7.81 (m, 11 H, Ar), 7.87 (d, J ϭ
14-(2-Naphthyl)-15H-benzo[h]benzo[6,7]indolo[3,2-b]quinoline (5f):
Method B: Starting with (2-naphthyl)acetonitrile (3f; 0.08 g,
0.50 mmol), 5f was isolated as a yellow solid (0.20 g, 89%). Method
A: Starting with 4f (0.13 g, 0.28 mmol), 5f was isolated as a yellow
solid (0.07 g, 54%). 1H NMR (250 MHz, CDCl3): δ ϭ 7.38Ϫ7.98
(m, 15 H, Ar), 8.06 (d, 3J ϭ 7.4 Hz, 1 H, Ar), 8.14 (s, 1 H, Ar),
8.6 Hz, 1 H, Ar), 8.03Ϫ8.06 (m, 2 H, Ar), 8.58 (br. s, 1 H, NH),
8.67 (d, 3J ϭ 8.6 Hz, 1 H, Ar), 9.74 (d, 3J ϭ 8.1 Hz, 1 H, Ar) ppm.
13C NMR (50.3 MHz, CDCl3): δ ϭ 21.63 (ArCH3), 119.84, 120.72
(CH), 120.83 (C), 121.00 (CH), 122.20 (C), 123.16, 124.80, 125.68,
126.05, 126.51, 126.68, 127.23, 127.26, 127.52 (CH), 128.01, 128.14
(C), 129.13, 129.28, 129.54 (CH), 130.02 (C), 130.81 (CH), 132.36,
132.40, 133.77, 134.03, 134.53, 139.14, 139.20, 143.29 (C) ppm. IR
(KBr): ν˜ ϭ 3440 (s), 3050 (m), 2951 (w), 2921 (w), 1673 (m), 1630
(m), 1600 (m), 1531 (m), 1515 (m), 1487 (m), 1464 (m), 1449 (m),
1441 (m), 1382 (s), 1332 (m), 1285 (m), 1197 (m), 1166 (m), 827
(m), 802 (m), 766 (s) cmϪ1. Fluorescence (CH3CN): Ex (Fλmax) ϭ
380 (445.92) nm. UV/Vis (CH3CN): λmax (lg ε) ϭ 381.6 nm (4.41),
363.2 (4.28), 306.5 (4.82), 267.7 (4.49), 260.7 (4.50), 242.6 (4.53),
216.1 (4.71). MS (EI, 70 eV): m/z (%) ϭ 408 (100) [M]ϩ, 204 (10),
196 (15), 143 (52). The exact molecular mass (m/z ϭ 408.1626 Ϯ 2
mD [Mϩ]) for C30H20N2 was confirmed by HRMS (EI, 70 eV).
3
3
8.47 (br. s, 1 H, NH), 8.57 (d, J ϭ 8.8 Hz, 1 H, Ar), 9.66 (d, J ϭ
8.1 Hz, 1 H, Ar) ppm. 13C NMR (50.3 MHz, CDCl3): δ ϭ 118.06
(C), 119.75, 120.66 (CH), 120.79 (C), 121.02 (CH), 122.24 (C),
123.05, 124.74, 125.67, 126.12, 126.49, 126.68, 126.94, 126.96,
127.22, 127.56 (CH), 127.66 (C), 127.87, 128.01, 128.24, 129.07,
129.10, 129.39 (CH), 130.15, 132.11, 132.18, 132.32, 133.21, 133.62,
133.98, 135.72, 139.14, 142.66 (C) ppm. IR (KBr): ν˜ ϭ 3462 (m),
3052 (m), 2961 (w), 2925 (w), 1630 (w), 1598 (m), 1564 (m), 1532
(m), 1506 (m), 1466 (m), 1437 (m), 1382 (s), 1324 (m), 1284 (m),
1262 (s), 1197 (s), 1173 (m), 1092 (m), 1017 (m), 824 (s), 797 (s),
764 (s), 747 (m) cmϪ1. Fluorescence (CH3CN): Ex (Fλmax) ϭ 380
(452.47) nm. UV/Vis (CH3CN): λmax (lg ε) ϭ 382.2 nm (4.23), 364.1
(4.10), 307.2 (4.66), 260.9 (4.47), 243.0 (4.52), 236.6 (4.51), 224.1
(4.60). MS (EI, 70 eV): m/z (%) ϭ 444 (100) [M]ϩ, 222 (24), 167
(6), 83 (16).
14-(4-Tolyl)-15H-benzo[h]benzo[6,7]indolo[3,2-b]quinoline (5d):
Method B: Starting with 4-tolylacetonitrile (3d; 0.13 g, 1.00 mmol),
5d was isolated as a yellow solid (0.29 g, 71%). Method A: Starting
with 4d (0.10 g, 0.22 mmol), 5d was isolated as a yellow solid
1
(0.05 g, 60%). H NMR (250 MHz, [D6]DMSO): δ ϭ 2.49 (s, 3 H,
14-(4-Nitrophenyl)-15H-benzo[h]benzo[6,7]indolo[3,2-b]quinoline
(5g): Starting with (4-nitrophenyl)acetonitrile (3g; 0.08 g,
0.50 mmol), 5g was isolated as an orange solid (0.14 g, 62%). 1H
3
ArCH3), 7.46Ϫ7.81 (m, 11 H, Ar), 7.83 (d, J ϭ 7.8 Hz, 1 H, Ar),
8.04Ϫ8.10 (m, 1 H, Ar), 8.56 (d, J ϭ 8.6 Hz, 1 H, Ar), 8.89Ϫ8.94
3
(m, 1 H, Ar), 9.61 (d, 3J ϭ 7.7 Hz, 1 H, Ar), 11.77 (br. s, 1 H,
NH) ppm. 13C NMR (50.3 MHz, [D6]DMSO): δ ϭ 20.94 (ArCH3),
116.64 (C), 118.89, 120.39 (CH), 121.36, 121.94 (C), 123.12, 123.25,
124.08, 125.40, 126.11, 126.56, 127.15, 127.52, 128.03 (CH), 128.38
(C), 128.49, 129.50 (CH), 130.21 (C), 130.30 (CH), 131.09, 131.60,
131.76, 133.66, 137.66, 140.29, 141.25, 142.73 (C) ppm. IR (KBr):
ν˜ ϭ 3463 (s), 3049 (m), 1685 (w), 1674 (w), 1631 (w), 1599 (w),
1531 (m), 1511 (s), 1493 (m), 1466 (m), 1453 (m), 1438 (m), 1421
(m), 1381 (s), 1331 (m), 1284 (m), 1195 (m), 1184 (m), 826 (m), 798
(m), 786 (m), 765 (s), 567 (m) cmϪ1. Fluorescence (CH3CN): Ex
(Fλmax) ϭ 380 (444.97) nm. UV/Vis (CH3CN): λmax (lg ε) ϭ 381.6
nm (4.38), 363.1 (4.26), 306.7 (4.82), 268.0 (4.48), 260.5 (4.49),
243.6 (4.48). MS (EI, 70 eV): m/z (%) ϭ 408 (100) [M]ϩ, 204 (10),
196 (15), 143 (52). The exact molecular mass (m/z ϭ 408.1626 Ϯ 2
mD [Mϩ]) for C30H20N2 was confirmed by HRMS (EI, 70 eV).
3
NMR (250 MHz, [D6]DMSO): δ ϭ 7.57 (d, J ϭ 9.1 Hz, 1 H, Ar),
3
4
7.62Ϫ7.68 (m, 2 H, Ar), 7.74 (dd, J ϭ 7.7, J ϭ 1.4 Hz, 1 H, Ar),
7.83 (d, 3J ϭ 9.1 Hz, 3 H, Ar), 7.99 (d, 3J ϭ 9.0 Hz, 3 H, Ar),
3
4
8.09Ϫ8.14 (m, 1 H, Ar), 8.56 (dd, J ϭ 8.7, J ϭ 2.2 Hz, 3 H, Ar),
3
8.77Ϫ8.82 (m, 1 H, Ar), 9.59 (d, J ϭ 8.3 Hz, 1 H, Ar), 11.83 (br.
s, 1 H, NH) ppm. 13C NMR (50.3 MHz, [D6]DMSO): δ ϭ 116.43
(C), 118.86, 120.61 (CH), 121.13, 121.25 (C), 122.42, 122.96,
123.99, 124.02, 125.58 (CH), 125.94 (C), 126.12, 126.77, 126.82,
127.34, 127.65, 128.60 (CH), 129.82, 131.46, 131.72 (C), 132.17
(CH), 133.72, 140.55, 141.01, 141.39, 142.95, 147.66 (C) ppm. IR
(KBr): ν˜ ϭ 3428 (s), 3388 (s), 1652 (m), 1594 (w), 1505 (m), 1379
(m), 1342 (m), 1181 (m), 1147 (m), 1048 (s), 1026 (s), 1001 (s), 822
(w), 789 (m), 767 (s), 670 (m) cmϪ1. UV/Vis (CH3CN): λmax (lg ε) ϭ
383.1 nm (3.73), 365.0 (3.63), 302.6 (4.21), 265.4 (4.02), 242.5
(3.92). MS (EI, 70 eV): m/z (%) ϭ 439 (100) [M]ϩ, 393 (30), 219
(4), 196 (10). MS (ESI): 441 (30) [M ϩ 2 H]2ϩ, 440 (100) [M ϩ
H]ϩ, 439 (30) [M]Ϫ, 438 (100) [M Ϫ H]2Ϫ. The exact molecular
mass [M ϩ H]ϩ for C29H17N3O2 was confirmed by ESI-HRMS:
14-(4-Methoxyphenyl)-15H-benzo[h]benzo[6,7]indolo[3,2-b]quinoline
(5e): Method B: Starting with (4-methoxyphenyl)acetonitrile (3e;
0.15 g, 1.00 mmol), 5e was isolated as a yellow solid (0.38 g, 90%).
Method A: Starting with 4e (0.07 g, 0.15 mmol), 5e was isolated as calcd. 440.13935; found 440.13960.
5024  2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2004, 5020Ϫ5026

Efficient Synthesis of Fluorescent 15H-Benzo[h]benzo[6,7]indolo[3,2-b]quinolines
FULL PAPER
14-(2-Cyanophenyl)-15H-benzo[h]benzo[6,7]indolo[3,2-b]quinoline
(5h): Starting with (2-cyanophenyl)acetonitrile (3h; 0.07 g,
0.50 mmol), 5h was isolated as a yellow solid (0.20 g, 96%). 1H
NMR (250 MHz, CDCl3): δ ϭ 7.34 (d, 3J ϭ 9.1 Hz, 1 H, Ar),
7.38Ϫ7.98 (m, 13 H, Ar), 8.40 (br. s, 1 H, NH), 8.57 (d, 3J ϭ
(81Br)]ϩ, 474 (30) [M (79Br) ϩ H]ϩ, 473 (100) [M (79Br)]ϩ. The
exact molecular mass [M ϩ H]ϩ for C29H17BrN2 was confirmed
by ESI-HRMS: calcd. 473.06479; found 473.06465.
1,4-Bis(15H-benzo[h]benzo[6,7]indolo[3,2-b]quinolinyl)benzene (6):
The reaction was carried out according to the general procedure.
Starting with 1,4-bis(cyanomethyl)benzene (0.08 g, 0.50 mmol), 2
(0.38 g, 1.00 mmol) and sodium hydride (0.07 g, 3.00 mmol), 6 was
3
8.5 Hz, 1 H, Ar), 9.62 (d, J ϭ 8.1 Hz, 1 H, Ar) ppm. 13C NMR
(50.3 MHz, CDCl3): δ ϭ 114.47, 117.08, 117.80 (C), 119.75, 120.66
(CH), 120.98 (C), 121.60, 122.03, 124.97, 125.81, 126.70, 127.01,
127.15, 127.48, 127.65, 129.27, 129.46 (CH), 129.87, 131.05 (C),
131.84 (CH), 132.37, 132.46 (C), 133.46, 133.99 (CH), 134.27,
134.36, 138.73, 139.59, 142.60, 143.44 (C) ppm. IR (KBr): ν˜ ϭ 3326
(m), 3051 (w), 2229 (w), 1685 (m), 1673 (s), 1597 (m), 1532 (m),
1517 (m), 1491 (s), 1468 (m), 1438 (m), 1385 (s), 1332 (m), 1194
(m), 1180 (m), 825 (m), 799 (m), 765 (s), 743 (m) cmϪ1. Fluor-
1
isolated, after chromatography, as a yellow solid (0.34 g, 94%). H
NMR (600 MHz, CDCl3): δ ϭ 7.56Ϫ7.64 (m, 8 H, Ar), 7.65Ϫ7.85
3
(m, 10 H, Ar), 7.88 (d, J ϭ 7.8 Hz, 4 H, Ar), 7.96Ϫ8.03 (m, 4 H,
Ar), 8.66 (d, 3J ϭ 8.6 Hz, 1 H, Ar), 9.73 (d, 3J ϭ 8.2 Hz, 1 H, Ar),
10.90 (br. s, 2 H, NH) ppm. 13C NMR (150.8 MHz, CDCl3,
100 °C): δ ϭ 118.55, 121.63, 121.93, 123.80, 124.93, 125.66, 125.71,
126.01, 126.17, 127.16, 127.66 (CH), 130.78, 131.92, 133.95 (C)
ppm. Low signal/noise ratio, due to low solubility in many organic
solvents. MS (ESI): m/z (%) ϭ 1420 (35) [2 M ϩ H]ϩ, 711 (100)
[M ϩ H]ϩ, 434 (40). The exact molecular mass [M ϩ H]ϩ for
C52H30N4 was confirmed by ESI-HRMS: calcd. 711.25432; found
711.25440. C52H30N4 (710.84): calcd. C 87.86, H 4.25, N 7.88;
found C 87.57, H 4.43, N 7.66.
escence (CH3CN): Ex (Fλmax) ϭ 380 (471.64) nm. UV/Vis
(CH3CN): λmax (lg ε) ϭ 383.9 nm (4.34), 365.3 (4.21), 306.1 (4.71),
262.0 (4.47), 241.9 (4.47), 231.4 (4.52). MS (EI, 70 eV): m/z (%) ϭ
419 (100) [M]ϩ, 209 (16). The exact molecular mass (m/z ϭ
419.1422 Ϯ 2 mD [Mϩ]) for C30H17N3 was confirmed by HRMS
(EI, 70 eV).
14-(3-Bromophenyl)-15H-benzo[h]benzo[6,7]indolo[3,2-b]quinoline
(5i): Starting with (3-bromophenyl)acetonitrile 3i (0.10 g,
0.50 mmol), 5i was isolated as a yellow solid (0.23 g, 95%). 1H
NMR (250 MHz, CDCl3): δ ϭ 7.40Ϫ7.68 (m, 5 H, Ar), 7.71Ϫ7.87
(m, 6 H, Ar), 8.03Ϫ8.07 (m, 3 H, Ar), 8.46 (br. s, 1 H, NH), 8.63
Acknowledgments
We thank Mrs Rita Schroeder for experimental contributions. Fin-
ancial support from the Konrad-Adenauer-Stiftung (scholarship
for J. T. A.) and the Deutsche Forschungsgemeinschaft is grate-
fully acknowledged.
(d, J ϭ 8.7 Hz, 1 H, Ar), 9.70 (d, J ϭ 8.0 Hz, 1 H, Ar) ppm. 13C
NMR (50.3 MHz, CDCl3): δ ϭ 118.29 (C), 119.73, 120.65 (CH),
120.93 (C), 121.30 (CH), 121.92 (C), 122.49 (CH), 123.62 (C),
124.88, 125.80 (CH), 126.04 (C), 126.51, 126.61, 126.80, 127.34,
127.59, 128.96, 129.20 (CH), 129.79 (C), 130.92, 131.97 (CH),
132.30, 132.39 (C), 133.20 (CH), 134.22, 136.98, 139.27, 142.78,
143.51 (C) ppm. IR (KBr): ν˜ ϭ 3439 (m), 3050 (m), 1631 (w), 1594
(m), 1560 (m), 1531 (m), 1517 (m), 1468 (s), 1451 (m), 1439 (m),
1418 (m), 1405 (m), 1383 (s), 1360 (m), 1330 (m), 1286 (m), 1191
(m), 1073 (w), 814 (m), 801 (m), 765 (s), 692 (m) cmϪ1. Fluor-
3
3
[1]
[1a]
´ ´
J.-Y. Merour, A. Merour, Synthesis 1994, 767
δ-Carbolines:
and references cited therein; for β-carbolines, see: [1b] J. Kobay-
ashi, J.-F. Cheng, T. Ohta, S. Nozoe, Y. Ohizumi, T. Sasaki, J.
[1c]
Org. Chem. 1990, 55, 3666.
T. G. Hagen, K. F. Koehler, P.
W. Codding, P. Skolnick, J. M. Cook, J. Med. Chem. 1990,
[1d]
33, 2343.
P. Rocca, F. Marsais, A. Godard, G. Queguiner,
Tetrahedron 1993, 46, 3325.
[2]
[3]
K. Cimanga, T. De Bruyne, L. Pieters, M. Claeys, A. Vlietinck,
Tetrahedron Lett. 1996, 37, 1703.
escence (CH3CN): Ex (Fλmax) ϭ 385 (453.08) nm. UV/Vis
S. C. Benson, J. E. Li, J. K. Snyder, J. Org. Chem. 1992, 57,
(CH3CN): λmax (lg ε) ϭ 382.6 nm (4.41), 364.2 (4.29), 306.4 (4.82),
261.3 (4.53), 242.5 (4.57), 235.0 (4.57), 215.6 (4.71). MS (EI, 70
eV): m/z (%) ϭ 474 (100) [M]ϩ, 472 (100) [M]ϩ, 393 (24), 196 (40).
MS (ESI): m/z (%) ϭ 969 (20) [2 M ϩ Na]ϩ, 944 (20) [2 M Ϫ 2
H]2Ϫ, 475 (100) [M (81Br)]ϩ, 473 (80) [M (79Br)]Ϫ, 471 (100) [M Ϫ
2 H]2Ϫ. The exact molecular mass [M ϩ H]ϩ for C29H17BrN2 was
confirmed by ESI-HRMS: calcd. 473.06479; found 473.06441.
5285.
[4] [4a]
K. N. Kilminster, M. Sainsbury, J. Chem. Soc., Perkin
[4b]
Trans. 1 1972, 2264.
Y. Oikawa, O. Yonemitsu, J. Chem.
Soc., Perkin Trans. 1 1976, 1479.
[5]
P. Langer, J. T. Anders, K. Weisz, J. Jähnchen, Chem. Eur. J.
2003, 9, 3951.
[6] [6a]
A. N. Tackie, G. L. Boye, M. H. M. Sharaf, P. L. Schiff Jr.,
R. C. Crouch, T. D. Spitzer, R. L. Johnson, J. Dunn, D. Min-
14-(4-Bromophenyl)-15H-benzo[h]benzo[6,7]indolo[3,2-b]quinoline
(5j): Starting with (4-bromophenyl)acetonitrile (4j; 0.10 g,
0.50 mmol), 5j was isolated as a yellow solid (0.23 g, 96%). 1H
NMR (250 MHz, CDCl3): δ ϭ 7.40Ϫ7.68 (m, 7 H, Ar), 7.71Ϫ7.87
(m, 5 H, Ar), 8.03Ϫ8.07 (m, 2 H, Ar), 8.46 (br. s, 1 H, NH), 8.63
ick, J. Nat. Prod. 1993, 56, 653. [6b] J. L. Pousset, M.-T. Martin,
[6c]
A. Jossang, B. Bodo, Phytochemistry 1995, 39, 735.
S. Y.
Ablordeppey, P. Fan, A. M. Clark, A. Nimrod, Bioorg. Med.
Chem. 1999, 7, 343. [6d] P. Fan, S. Y. Ablordeppey, J. Heterocycl.
[6e]
Chem. 1997, 34, 1789.
Acta 2002, 85, 3823.
T.-L. Ho, D.-G. Jou, Helv. Chim.
(d, J ϭ 8.7 Hz, 1 H, Ar), 9.70 (d, J ϭ 8.0 Hz, 1 H, Ar) ppm. 13C
NMR (50.3 MHz, CDCl3): δ ϭ 116.48 (C), 118.88, 120.52 (CH),
121.26, 121.57, 122.10 (C), 122.75, 123.07, 124.03, 125.53, 125.80,
126.71, 126.73 (CH), 126.98 (C), 127.28, 127.61, 128.57 (CH),
130.02, 131.48, 131.74 (C), 131.94, 132.65 (CH), 133.32, 133.68,
140.33, 141.10, 142.75 (C) ppm. IR (KBr): ν˜ ϭ 3442 (s), 3051 (m),
1679 (m), 1631 (m), 1597 (m), 1567 (m), 1531 (m), 1487 (s), 1466
(m), 1438 (m), 1421 (m), 1383 (s), 1360 (m), 1331 (m), 1286 (m),
1243 (m), 1185 (s), 1070 (m), 1012 (m), 837 (m), 822 (s), 797 (s),
764 (s) cmϪ1. Fluorescence (CH3CN): Ex (Fλmax) ϭ 385 (451.64)
nm. UV/Vis (CH3CN): λmax (lg ε) ϭ 382.2 nm (4.39), 364.0 (4.27),
307.9 (4.80), 261.4 (4.54), 242.8 (4.55), 217.1 (4.67). MS (EI, 70
eV): m/z (%) ϭ 474 (100) [M]ϩ, 472 (100) [M]ϩ, 392 (28), 196 (44).
MS (ESI): m/z (%) ϭ 476 (30) [M (81Br) ϩ H]ϩ, 475 (100) [M
3
3
[7] [7a]
M. M. Cooper, J. M. Lovell, J. A. Joule, Tetrahedron Lett.
[7b]
1996, 37, 4283.
K. Cimanga, T. D. Bruyne, L. Pieters, M.
Claeys, A. J. Vlietinck, Tetrahedron Lett. 1996, 37, 1703.
Dwuma-Badu, J. S. K. Ayim, N. I. Y. Fiagbe, J. E. Knapp, D.
[7c]
D.
L. Schiff Jr., D. J. Slatkin, J. Pharm. Sci. 1978, 67, 433.
[8] [8a]
A. O. Oyekan, S. Y. Ablordeppey, Med. Chem. Res. 1996,
6, 602. [8b] S. Y. Ablordeppey, P. Fan, J. Heterocycl. Chem. 1997,
34, 1789.
[8c]
K. Cimanga, T. D. Bruyne, A. Lasure, B. V. Poel,
L. Pieters, M. Claeys, D.-V. Berghe, K. Kambu, L. Tona, A. J.
Vlietinck, Planta Med. 1996, 62, 22. [8d] M. Singh, M. P. Singh,
[8e]
S. Y. Ablordeppey, Drug. Dev. Ind. Pharm. 1996, 22, 379.
K. Boakye-Yiadom, S. M. Herman Ackah, J. Pharm. Sci. 1979,
68, 1510.
[9a] A. Polak, Prog. Drug. Res. 1997, 49, 219. [9b] V. S. Georgiev,
Med. Chem. Res. 1993, 13, 493.
[9]
Eur. J. Org. Chem. 2004, 5020Ϫ5026
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5025

J. T. Anders, P. Langer
FULL PAPER
[10]
[13]
[14]
[13a]
S. Y. Ablordeppey, P. Fan, A. M. Clark, A. Nimrod, Bioorg.
For reviews of domino and sequential reactions, see:
L. F.
Tietze, U. Beifuss, Angew. Chem. 1993, 105, 137; Angew. Chem.
Int. Ed. Engl. 1993, 32, 131. [13b] L. F. Tietze, Chem. Rev. 1996,
96, 115.
Med. Chem. 1999, 7, 343.
[11] [11a]
P. Langer, J. Wuckelt, M. Döring, H. Görls, J. Org. Chem.
[11b]
2000, 65, 3603.
P. Langer, J. T. Anders, Eur. J. Org. Chem.
2001, 3953.
D. Lindauer, R. Beckert, M. Döring, P. Fehling, H. Görls, J.
Prakt. Chem. 1995, 337, 143.
[12]
For a review of oxaldiimidoyl dichlorides, see: P. Langer, M.
Döring, Eur. J. Org. Chem. 2002, 221.
Received June 8, 2004
5026
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 5020Ϫ5026